Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21179 | 63760;63761;63762 | chr2:178587774;178587773;178587772 | chr2:179452501;179452500;179452499 |
| N2AB | 19538 | 58837;58838;58839 | chr2:178587774;178587773;178587772 | chr2:179452501;179452500;179452499 |
| N2A | 18611 | 56056;56057;56058 | chr2:178587774;178587773;178587772 | chr2:179452501;179452500;179452499 |
| N2B | 12114 | 36565;36566;36567 | chr2:178587774;178587773;178587772 | chr2:179452501;179452500;179452499 |
| Novex-1 | 12239 | 36940;36941;36942 | chr2:178587774;178587773;178587772 | chr2:179452501;179452500;179452499 |
| Novex-2 | 12306 | 37141;37142;37143 | chr2:178587774;178587773;178587772 | chr2:179452501;179452500;179452499 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs772529311  |
0.108 | 0.011 | N | 0.239 | 0.213 | 0.28798054836 | gnomAD-2.1.1 | 1.24E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 1.82E-05 | 0 |
| S/G | rs772529311 |
0.108 | 0.011 | N | 0.239 | 0.213 | 0.28798054836 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/G | rs772529311 |
0.108 | 0.011 | N | 0.239 | 0.213 | 0.28798054836 | gnomAD-4.0.0 | 6.85293E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.73129E-05 | None | 0 | 0 | 5.95919E-06 | 0 | 1.61119E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1094 | likely_benign | 0.1145 | benign | -0.263 | Destabilizing | 0.693 | D | 0.421 | neutral | None | None | None | None | I |
| S/C | 0.2849 | likely_benign | 0.2896 | benign | -0.148 | Destabilizing | 0.999 | D | 0.512 | neutral | N | 0.495919772 | None | None | I |
| S/D | 0.5678 | likely_pathogenic | 0.5354 | ambiguous | 0.188 | Stabilizing | 0.916 | D | 0.496 | neutral | None | None | None | None | I |
| S/E | 0.6422 | likely_pathogenic | 0.6326 | pathogenic | 0.099 | Stabilizing | 0.957 | D | 0.496 | neutral | None | None | None | None | I |
| S/F | 0.5505 | ambiguous | 0.5129 | ambiguous | -0.818 | Destabilizing | 0.996 | D | 0.5 | neutral | None | None | None | None | I |
| S/G | 0.1095 | likely_benign | 0.1151 | benign | -0.387 | Destabilizing | 0.011 | N | 0.239 | neutral | N | 0.483549508 | None | None | I |
| S/H | 0.5983 | likely_pathogenic | 0.6024 | pathogenic | -0.836 | Destabilizing | 0.999 | D | 0.498 | neutral | None | None | None | None | I |
| S/I | 0.5031 | ambiguous | 0.4741 | ambiguous | -0.069 | Destabilizing | 0.994 | D | 0.493 | neutral | N | 0.495412793 | None | None | I |
| S/K | 0.8905 | likely_pathogenic | 0.8952 | pathogenic | -0.44 | Destabilizing | 0.916 | D | 0.497 | neutral | None | None | None | None | I |
| S/L | 0.2516 | likely_benign | 0.2346 | benign | -0.069 | Destabilizing | 0.987 | D | 0.463 | neutral | None | None | None | None | I |
| S/M | 0.3476 | ambiguous | 0.3589 | ambiguous | 0.093 | Stabilizing | 0.999 | D | 0.506 | neutral | None | None | None | None | I |
| S/N | 0.2152 | likely_benign | 0.2175 | benign | -0.102 | Destabilizing | 0.892 | D | 0.503 | neutral | N | 0.50317378 | None | None | I |
| S/P | 0.6344 | likely_pathogenic | 0.5836 | pathogenic | -0.104 | Destabilizing | 0.996 | D | 0.507 | neutral | None | None | None | None | I |
| S/Q | 0.6549 | likely_pathogenic | 0.682 | pathogenic | -0.324 | Destabilizing | 0.996 | D | 0.487 | neutral | None | None | None | None | I |
| S/R | 0.8774 | likely_pathogenic | 0.8721 | pathogenic | -0.228 | Destabilizing | 0.983 | D | 0.496 | neutral | D | 0.522452975 | None | None | I |
| S/T | 0.1047 | likely_benign | 0.1076 | benign | -0.203 | Destabilizing | 0.944 | D | 0.504 | neutral | N | 0.51158262 | None | None | I |
| S/V | 0.3915 | ambiguous | 0.3891 | ambiguous | -0.104 | Destabilizing | 0.987 | D | 0.509 | neutral | None | None | None | None | I |
| S/W | 0.7157 | likely_pathogenic | 0.6623 | pathogenic | -0.866 | Destabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | I |
| S/Y | 0.5204 | ambiguous | 0.4761 | ambiguous | -0.573 | Destabilizing | 0.996 | D | 0.498 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.